Universidad del Desarrollo

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Contemporary Clinical and Molecular Epidemiology of Vancomycin-Resistant Enterococcal Bacteremia: A Prospective Multicenter Cohort Study (VENOUS I)
(2021)
German A Contreras
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MUNITA SEPULVEDA, JOSE MANUEL
;
Shelby Simar
;
Courtney Luterbach
;
An Q Dinh
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Vancomycin-resistant enterococci (VRE) are major therapeutic challenges. Prospective contemporary data characterizing the clinical and molecular epidemiology of VRE bloodstream infections (BSIs) are lacking.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>The Vancomycin-Resistant Enterococcal BSI Outcomes Study (VENOUS I) is a prospective observational cohort of adult patients with enterococcal BSI in 11 US hospitals. We included patients with Enterococcus faecalis or Enterococcus faecium BSI with ≥1 follow-up blood culture(s) within 7 days and availability of isolate(s) for further characterization. The primary study outcome was in-hospital mortality. Secondary outcomes were mortality at days 4, 7, 10, 12, and 15 after index blood culture. A desirability of outcome ranking was constructed to assess the association of vancomycin resistance with outcomes. All index isolates were subjected to whole genome sequencing.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Forty-two of 232 (18%) patients died in hospital and 39 (17%) exhibited microbiological failure (lack of clearance in the first 4 days). Neutropenia (hazard ratio [HR], 3.13), microbiological failure (HR, 2.4), VRE BSI (HR, 2.13), use of urinary catheter (HR, 1.85), and Pitt BSI score ≥2 (HR, 1.83) were significant predictors of in-hospital mortality. Microbiological failure was the strongest predictor of in-hospital mortality in patients with E faecium bacteremia (HR, 5.03). The impact of vancomycin resistance on mortality in our cohort changed throughout the course of hospitalization. Enterococcus faecalis sequence type 6 was a predominant multidrug-resistant lineage, whereas a heterogeneous genomic population of E faecium was identified.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Failure of early eradication of VRE from the bloodstream is a major factor associated with poor outcomes.</jats:p> </jats:sec>
5Scopus© Citations 42
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Detection of heterogeneous vancomycin intermediate resistance in MRSA isolates from Latin America
(2020)
Betsy E Castro
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Maritza Berrio
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Monica L Vargas
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Lina P Carvajal
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Lina V Millan
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Vancomycin is a common first-line option for MRSA infections. The heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) phenotype is associated with therapeutic failure. However, hVISA isolates are usually reported as vancomycin susceptible by routine susceptibility testing procedures.</jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p>To detect and characterize the hVISA phenotype in MRSA isolates causing infections in nine Latin American countries.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We evaluated a total of 1189 vancomycin-susceptible MRSA isolates recovered during 2006–08 and 2011–14. After an initial screening of hVISA using glycopeptide-supplemented agar strategies, the detection of hVISA was performed by Etest (GRD) and Macro-method (MET). Isolates deemed to be hVISA were subjected to population analysis profile/AUC (PAP/AUC) and WGS for further characterization. Finally, we interrogated alterations in predicted proteins associated with the development of the VISA phenotype in both hVISA and vancomycin-susceptible S. aureus (VSSA) genomes.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 39 MRSA isolates (3.3%) were classified as hVISA (1.4% and 5.6% in MRSA recovered from 2006–08 and 2011–14, respectively). Most of the hVISA strains (95%) belonged to clonal complex (CC) 5. Only 6/39 hVISA isolates were categorized as hVISA by PAP/AUC, with 6 other isolates close (0.87–0.89) to the cut-off (0.9). The majority of the 39 hVISA isolates exhibited the Leu-14→Ile (90%) and VraT Glu-156→Gly (90%) amino acid substitutions in WalK. Additionally, we identified 10 substitutions present only in hVISA isolates, involving WalK, VraS, RpoB and RpoC proteins.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The hVISA phenotype exhibits low frequency in Latin America. Amino acid substitutions in proteins involved in cell envelope homeostasis and RNA synthesis were commonly identified. Our results suggest that Etest-based methods are an important alternative for the detection of hVISA clinical isolates.</jats:p></jats:sec>
3 1Scopus© Citations 14
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Failure of High-Dose Daptomycin for Bacteremia Caused by Daptomycin-Susceptible Enterococcus faecium Harboring LiaSR Substitutions
(2014)
MUNITA SEPULVEDA, JOSE MANUEL
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Nagendra N. Mishra
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Danya Alvarez
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Truc T. Tran
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Lorena Diaz
13 1Scopus© Citations 57
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Influence of Inoculum Effect on the Efficacy of Daptomycin Monotherapy and in Combination with beta-Lactams against Daptomycin-Susceptible Enterococcus faecium Harboring LiaSR Substitutions
(2018)
Razieh Kebriaei
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Seth A. Rice
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Kavindra V. Singh
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Kyle C. Stamper
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An Q. Dinh
<jats:p> <jats:named-content content-type="genus-species">Enterococcus faecium</jats:named-content> isolates that harbor LiaFSR substitutions but are phenotypically susceptible to daptomycin (DAP) by current breakpoints are problematic, since predisposition to resistance may lead to therapeutic failure. Using a simulated endocardial vegetation (SEV) pharmacokinetic/pharmacodynamic (PK/PD) model, we investigated DAP regimens (6, 8, and 10 mg/kg of body weight/day) as monotherapy and in combination with ampicillin (AMP), ceftaroline (CPT), or ertapenem (ERT) against <jats:named-content content-type="genus-species">E. faecium</jats:named-content> HOU503, a DAP-susceptible strain that harbors common LiaS and LiaR substitutions found in clinical isolates (T120S and W73C, respectively). </jats:p>
3 1Scopus© Citations 37

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